This research proposal will combine in vitro and in vivo techniques together with an evaluation of nephronal fine structure, histochemistry and physiological parameters in investigations designed to elucidate the cell biology of normal and nephrotic kidneys. The roles played by cytoplasmic microtubules, microfilaments, and sialic acid surface coat and charge in normal, differentiating, and nephrotic kidneys will be investigated. Of particular interest will be the determination of possible deleterious effects of cold induced microtubule loss during in vitro preservation and how to prevent these effects. In vitro techniques for studying kidneys will be developed and the various environmental and physiogical parameters effecting such studies are to be investigated. Finally, a series of studies designed to elucidate mechanisms involved in the etiology of puromycin aminonucleoside nephrosis will be undertaken.